RESUMO
Evidence exists that motilin immunoreactivity is highly expressed in Purkinje cells. In this study, immunohistochemistry and whole-cell patch-clamp recording were performed to investigate the spatial distribution and electrophysiological effects of motilin receptors in the cerebellum. We show here that motilin receptors are strongly expressed in Purkinje cells of the human and rat cerebellum. Motilin at 10 nM depolarized Purkinje cells of the rat cerebellum, and this was mimicked by the motilin receptor agonist erythromycin. The depolarization evoked by motilin persisted in the presence of tetrodotoxin, glutamate and gamma-amino-n-butyric acid receptor antagonists, indicating that motilin excited the Purkinje cells by activating the receptor expressed on the neurons recorded. We suggest that motilin may serve specific neural functions in the cerebellum.
Assuntos
Cerebelo/citologia , Fármacos Gastrointestinais/farmacologia , Motilina/farmacologia , Células de Purkinje/efeitos dos fármacos , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo , 2-Amino-5-fosfonovalerato/análogos & derivados , 2-Amino-5-fosfonovalerato/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Eritromicina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Humanos , Técnicas In Vitro , Técnicas de Patch-Clamp , Células de Purkinje/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To study CD34, CD105, inducible nitric oxide synthase (iNOS), endogenous nitric oxide synthase (eNOS), and hypoxia-inducible factor 1 (HIF-1) alpha expression in human colorectal carcinomas. METHODS: The tissue microarrays (TMAs) were made up of 80 cases of colorectal carcinoma and 80 cases of non-neoplasm colorectal mucosa. The expression of CD34, CD105, NOS and HIF-1alpha was detected by immunohistochemistry (S-P). RESULTS: iNOS and HIF-1alpha expression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa (c2 = 43.166, P < 0.01; c2 = 10.4278, P < 0.01); eNOS expression in colorectal carcinoma was significantly lower than in non-neoplasm colorectal mucosa (c2 = 11.354, P < 0.01). The expression of iNOS correlated with differentiation (c2 = 18.141, P < 0.01), invasive depth (c2 = 4.748, P < 0.01), and Micro vessel density (MVD) (t = 2.327, P < 0.05). The expression of HIF-1alpha was correlated with infiltrating depth (c2 = 4.397, P < 0.05), Dukeos staging (c2 = 4.255, P < 0.05), and MVD (t = 2.272, P < 0.05). No correlation was found in eNOS expression. CONCLUSION: Over-expression of iNOS and HIF-1alpha in colorectal carcinoma is correlated with the biological character MVD.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Patológica/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos CD34/genética , Antígenos CD34/metabolismo , Neoplasias Colorretais/genética , Endoglina , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imuno-Histoquímica , Microcirculação , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo III/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Análise Serial de TecidosRESUMO
Increased knowledge of molecular alterations involved in gastric carcinogenesis has provided useful information for diagnosis and prediction. In this study, we investigated the clinicopathological significance of TFF3 expression and Her-2/neu status in gastric adenocarcinoma and explored the correlation between TFF3 expression and Her-2/neu status. A hundred and twenty-six (126) patients having undergone curative gastrectomy were enrolled. Immunohistochemistry for TFF3 was performed on tumor tissues and non-neoplastic resection margins. Her-2/neu status was assessed by immunohistochemical staining and fluorescence in situ hybridization (FISH) on tumor tissues. As a result, TFF3 expression and Her-2/neu positivity were detected in 46.8% and 11.9% of the cases, respectively. Patients with negative TFF3 exhibited longer survival than the positive group (P=0.0142), while patients with positive Her-2/neu only showed a tendency toward longer overall survival (P>0.05). However, Her-2/neu was significantly associated with improved disease-free survival (P=0.0234). Multivariate analysis demonstrated Her-2/neu and TFF3 to be independent prognostic indicators of recurrence, and a significantly poor prognosis for expression of TFF3 in patients with Her-2/neu negative tumors. TFF3 is an independent indicator for overall survival in gastric cancer, while Her-2/neu, as a marker of long time survival prediction, seems to be limited.
Assuntos
Adenocarcinoma/química , Adenocarcinoma/genética , Biomarcadores Tumorais/análise , Peptídeos/análise , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Gastrectomia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo , Resultado do Tratamento , Fator Trefoil-3Assuntos
Adenocarcinoma/metabolismo , Eritropoetina/metabolismo , Neoplasias Gástricas/metabolismo , Análise Serial de Tecidos/métodos , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Metástase Linfática , Microvasos/química , Microvasos/patologia , Pessoa de Meia-Idade , Estômago/química , Estômago/patologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: It has been demonstrated that certain NK-1 antagonists could reduce proliferation of several cancer cell lines, however, it is unknown whether SR140333 exerts proliferation inhibition in breast cancer cell line. METHODS: Immunohistochemical staining was carried out to investigate the immunolocation of NK-1 in breast cancer tissues and T47D cell line, thereafter, various concentrations of [Sar9, Met(O2)11]substance P and SR140333 were applied alone or combined. MTT assay was applied to detect cytoactivation and coulter counter was to detect growth curve. The Hoechst33258 staining was performed to detect apoptosis. RESULTS: We found that breast cancer and T47D cells bear positive expression of NK-1. SR140333 inhibited cell growth in a dose dependent manner. Furthermore, SR140333 could counteract [Sar9, Met(O2)11]substance P induced proliferation. Hoechst33258 staining revealed the presence of apoptosis after SR140333 treatment. CONCLUSIONS: Our study demonstrated SR140333 exert proliferation inhibition in breast cancer cell line T47D and indicates NK-1 play a central role in the substance P related cell proliferation in breast cancer.